This competing renewal of our Pediatric Center Grant will focus on fibrotic sequelae of childhood renal diseases. The first project, with Dr. Fogo as the PI will focus on tubular interstitial fibrosis mechanisms related to angiotensin and plasminogen activator inhibitor-1. The second project with Dr. Ichikawa as PI will focus on the function of the renin angiotensin system in the macrophage and its contribution to interstitial fibrosis. The third project, headed by Dr. Kon, will focus on the role of the renin angiotensin system in the macrophage in atherosclerosis. The fourth project headed by a new member of the center grant, Dr. Allison Eddy at the Children's and Regional Medical Center, Seattle, will focus on macrophage scavenger receptors and their processing of low density lipoproteins and impact on renal fibrosis. Three pilot projects include a clinical pilot study (Dr. Jabs, PI) to establish measures of carotid artery intima media thickness in children with chronic kidney disease as a marker of cardiovascular disease risk; a basic science study (Dr. Upadhya, PI) investigating pathogenesis of fibrosis in a model of polycystic kidney disease and lastly a pilot study (Dr. Matsusaka, PI) to determine mechanisms of podocyte injury in novel transgenic animal models with HIV infection. These projects will be supported by an animal genotyping and phenotyping core and administrative core.